Superior efficacy of St John's wort extract WS® 5570 compared to placebo in patients with major depression:: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]

Background: The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS (R) 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses. Methods: The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS (R) 5570 600 mg/day, 127 to WS (R) 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination. Results: After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS (R) 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS (R) 5570 groups were statistically superior to placebo. Significantly more patients in the WS (R) 5570 treatment groups than in the placebo group showed treatment response and remission. WS (R) 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS (R) 5570 1200 mg/day group than the WS (R) 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations. Conclusion: Hypericum perforatum extract WS (R) 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS (R) 5570 groups for the treatment of mild to moderate major depression.